BACKGROUND: Cardiovascular disease is a leading cause of death in patients with end-stage renal disease (ESRD). Hypertension is a major risk factor for cardiovascular complications in these patients. Angiotensin-converting enzyme (ACE) inhibitors are an effective treatment for hypertension in patients with ESRD and are known to improve prognosis in patients with chronic renal failure. We investigated their effect on mortality in patients undergoing long-term hemodialysis therapy. METHODS: Clinical data for patients on hemodialysis therapy between 1994 and 2000 were reviewed. Patients were grouped according to whether they had been treated with ACE inhibitors. RESULTS: Sixty patients had been treated with ACE inhibitors (treated group) and 66 patients had not (untreated group). Blood pressure reduction was not significantly different between the treated and untreated groups. Nevertheless, comparing the treated group with the untreated group, mortality was decreased significantly in the treated group, with a risk reduction of 52% (rate ratio [RR], 0.482; confidence interval [CI], 0.25 to 0.91; P < 0.0019). In treated patients 65 years or younger, the absolute risk reduction of mortality was 79% (RR, 0.211; CI, 0.08 to 0.58; P < 0.0006). CONCLUSION: Although further research is needed, these preliminary findings suggest that ACE inhibitors, independently of their antihypertensive effect, may dramatically reduce mortality among chronic hemodialysis patients 65 years or younger.